U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry MIXED
Molecular Formula C14H18N2O3
Molecular Weight 262.3049
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METHOHEXITAL

SMILES

CCC#CC(C)C1(CC=C)C(=NC(=O)N(C)C1=O)O

InChI

InChIKey=NZXKDOXHBHYTKP-UHFFFAOYSA-N
InChI=1S/C14H18N2O3/c1-5-7-8-10(3)14(9-6-2)11(17)15-13(19)16(4)12(14)18/h6,10H,2,5,9H2,1,3-4H3,(H,15,17,19)

HIDE SMILES / InChI
Methohexital is an ultrashort-acting barbiturate widely used in dentistry because of its rapid onset, predictable effects, and short duration of action. It was marked under the name brevital sodium for the intravenous anaesthesia. It has also been commonly used to induce deep sedation. Like other barbiturates, methohexital exerts its effects through the gamma-aminobutyric acid (GABA) receptor complex. By binding to its own receptor on the complex, methohexital augments the inhibitory effect of GABA on neurons and additionally can exert a similar effect independent of GABA.

Originator

Curator's Comment:: SM Chernish’s group at Lilly Research Laboratories (Indianapolis, USA) in 1956.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
BREVITAL SODIUM

Approved Use

Brevital Sodium can be used in adults as follows: For intravenous induction of anesthesia prior to the use of other general anesthetic agents. For intravenous induction of anesthesia and as an adjunct to subpotent inhalational anesthetic agents (such as nitrous oxide in oxygen) for short surgical procedures; Brevital Sodium may be given by infusion or intermittent injection. For use along with other parenteral agents, usually narcotic analgesics, to supplement subpotent inhalational anesthetic agents (such as nitrous oxide in oxygen) for longer surgical procedures. As intravenous anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli (see WARNINGS ). As an agent for inducing a hypnotic state. Brevital Sodium can be used in pediatric patients older than 1 month as follows: For rectal or intramuscular induction of anesthesia prior to the use of other general anesthetic agents. For rectal or intramuscular induction of anesthesia and as an adjunct to subpotent inhalational anesthetic agents for short surgical procedures. As rectal or intramuscular anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli.

Launch Date

-3.00240011E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.8 μg/mL
25 mg/kg single, rectal
dose: 25 mg/kg
route of administration: Rectal
experiment type: SINGLE
co-administered:
METHOHEXITAL plasma
Homo sapiens
population: HEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2.39 mg × h/L
2 mg/kg single, intravenous
dose: 2 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
METHOHEXITAL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2.24 mg × h/L
2 mg/kg single, intravenous
dose: 2 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
METHOHEXITAL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.71 mg × h/L
2 mg/kg single, intravenous
dose: 2 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
METHOHEXITAL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
151 min
2 mg/kg single, intravenous
dose: 2 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
METHOHEXITAL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
136 min
2 mg/kg single, intravenous
dose: 2 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
METHOHEXITAL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
204 min
2 mg/kg single, intravenous
dose: 2 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
METHOHEXITAL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
102 min
25 mg/kg single, rectal
dose: 25 mg/kg
route of administration: Rectal
experiment type: SINGLE
co-administered:
METHOHEXITAL plasma
Homo sapiens
population: HEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
27.1%
1 % single, intravenous
dose: 1 %
route of administration: Intravenous
experiment type: SINGLE
co-administered:
METHOHEXITAL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
30 mg/kg single, rectal
Dose: 30 mg/kg
Route: rectal
Route: single
Dose: 30 mg/kg
Sources:
unhealthy, 2.6 + 2.2 years
n = 648
Health Status: unhealthy
Age Group: 2.6 + 2.2 years
Population Size: 648
Sources:
Other AEs: Airways obstruction, Transient nocturnal oxygen desaturation...
Other AEs:
Airways obstruction (4%)
Transient nocturnal oxygen desaturation (4%)
Sources:
2 mg/mL single, intravenous
Dose: 2 mg/mL
Route: intravenous
Route: single
Dose: 2 mg/mL
Sources:
unhealthy, adult
Disc. AE: Seizures, Hepatic dysfunction NOS...
AEs leading to
discontinuation/dose reduction:
Seizures
Hepatic dysfunction NOS (severe)
Instability cardiovascular (severe)
Sources:
AEs

AEs

AESignificanceDosePopulation
Airways obstruction 4%
30 mg/kg single, rectal
Dose: 30 mg/kg
Route: rectal
Route: single
Dose: 30 mg/kg
Sources:
unhealthy, 2.6 + 2.2 years
n = 648
Health Status: unhealthy
Age Group: 2.6 + 2.2 years
Population Size: 648
Sources:
Transient nocturnal oxygen desaturation 4%
30 mg/kg single, rectal
Dose: 30 mg/kg
Route: rectal
Route: single
Dose: 30 mg/kg
Sources:
unhealthy, 2.6 + 2.2 years
n = 648
Health Status: unhealthy
Age Group: 2.6 + 2.2 years
Population Size: 648
Sources:
Seizures Disc. AE
2 mg/mL single, intravenous
Dose: 2 mg/mL
Route: intravenous
Route: single
Dose: 2 mg/mL
Sources:
unhealthy, adult
Hepatic dysfunction NOS severe
Disc. AE
2 mg/mL single, intravenous
Dose: 2 mg/mL
Route: intravenous
Route: single
Dose: 2 mg/mL
Sources:
unhealthy, adult
Instability cardiovascular severe
Disc. AE
2 mg/mL single, intravenous
Dose: 2 mg/mL
Route: intravenous
Route: single
Dose: 2 mg/mL
Sources:
unhealthy, adult
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer





Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Placental transfer of tubocurarine. Case report.
1968 Jun
Clinical studies on induction agents. 28. A further comparison of venous complications following thiopentone, methohexitone and propanidid.
1969 Aug
Methohexitone and propanidid. A comparative investigation of the side effects.
1969 Feb
Factors in arrhythmia during dental outpatient general anesthesia.
1970 Sep-Oct
Methohexitone and thiopentone. Response to stimuli and incidence of some side effects.
1971 Oct
Activation of the electroencephalogram with intravenous Brietal (methohexitone): the findings in 100 cases.
1971 Oct
A rare allergic reaction to sodium methohexital.
1972 Dec
Acute allergic reaction associated with methohexital anesthesia: report of six cases.
1972 Dec
Intramuscular sodium methohexital as a sole pediatric anesthetic-analgesic agent.
1972 Nov-Dec
A comparative study of etomidate and methohexital as induction agents for analgesic anesthesia.
1976
Methohexitone-induced convulsions in epileptics.
1977 Aug
Identification of speech lateralization by intracarotid injection of methohexital.
1978 Jul
Seizures induced by methohexital.
1981 Apr
The prevention of pain on injection. A study of the effect of intravenous lignocaine before methohexitone.
1981 Sep
[Electroclinical aspects of intramuscular methohexital anesthesia in children].
1982 Nov
Severe respiratory depression following pentazocine and methohexitone. A case report.
1982 Oct
Seizure duration in unilateral electroconvulsive therapy. A comparison of the anaesthetic agents etomidate and Althesin with methohexitone.
1984 Jun
Drugs as allergens: the molecular basis of IgE binding to thiopentone.
1987
[Generalized seizure induced by methohexital].
1987
Pain on injection of methohexitone. The use of lignocaine to modify pain on injection of methohexitone during anaesthesia for electroconvulsive therapy.
1989 Aug
Rectal methohexital causing apnea in two patients with meningomyeloceles.
1991 Jun
Spontaneous seizure after concurrent use of methohexital anesthesia for electroconvulsive therapy and paroxetine: a case report.
1995 Feb
A prospective study of rectal methohexital: efficacy and side effects in 648 cases.
1995 Nov
The comparative effects of methohexital, propofol, and etomidate for electroconvulsive therapy.
1995 Sep
A prospective evaluation of the safety and efficacy of methohexital in the emergency department.
1996 Jul
Clonidine and methohexital-induced epileptic magnetoencephalographic discharges in patients with focal epilepsies.
1998 Aug
Alfentanil decreases the excitatory phenomena of sodium methohexital.
1998 Sep
Acute detoxification of opioid-addicted patients with naloxone during propofol or methohexital anesthesia: a comparison of withdrawal symptoms, neuroendocrine, metabolic, and cardiovascular patterns.
2000 Apr
Inhibition of activator protein 1 by barbiturates is mediated by differential effects on mitogen-activated protein kinases and the small G proteins ras and rac-1.
2004 Dec
Effect of testosterone replacement or duration of castration on baroreflex bradycardia in conscious rats.
2005 Mar 30
Orchiectomy or androgen receptor blockade attenuates baroreflex-mediated bradycardia in conscious rats.
2006 Jan 23
Seizures during intracarotid methohexital and amobarbital testing.
2007 Feb
Colorectal distension-induced pseudoaffective changes as indices of nociception in the anesthetized female rat: morphine and strain effects on visceral sensitivity.
2007 Jul-Aug
Pulmonary response to intratracheal instillation of ultrafine versus fine titanium dioxide: role of particle surface area.
2008 Dec 1
Surface area of particle administered versus mass in determining the pulmonary toxicity of ultrafine and fine carbon black: comparison to ultrafine titanium dioxide.
2009 May 4
Transient global amnesia after ablation of premature ventricular beats arising from the right coronary cusp.
2010 Aug 15
Patents

Patents

Sample Use Guides

Dosage is highly individualized: the drug should be administered only by those completely familiar with its quantitative differences from other barbiturate anesthetics. Adult: brevital sodium (METHOHEXITAL SODIUM) is administered intravenously in a concentration of no higher than 1%. Higher concentrations markedly increase the incidence of muscular movements and irregularities in respiration and blood pressure. Induction of anesthesia: a 1% solution is administered at a rate of about 1 mL/5 seconds. Gaseous anesthetics and/or skeletal muscle relaxants may be administered concomitantly. The dose required for induction may range from 50 to 120 mg or more but averages about 70 mg. The usual dosage in adults ranges from 1 to 1.5 mg/kg. The induction dose usually provides anesthesia for 5 to 7 minutes. Maintenance of anesthesia: may be accomplished by intermittent injections of the 1% solution or, more easily, by continuous intravenous drip of a 0.2% solution. Intermittent injections of about 20 to 40 mg (2 to 4 mL of a 1% solution) may be given as required, usually every 4 to 7 minutes. For continuous drip, the average rate of administration is about 3 mL of a 0.2% solution/minute (1 drop/second). The rate of flow must be individualized for each patient. For longer surgical procedures, gradual reduction in the rate of administration is recommended Pediatric Patients: Brevital Sodium is administered intramuscularly in a 5% concentration and administered rectally as a 1% solution. Induction of anesthesia: by the intramuscular route of administration, the usual dose ranges from 6.6 to 10 mg/kg of the 5% concentration. For rectal administration, the usual dose for induction is 25 mg/kg using the 1% solution.
Route of Administration: Other
In Vitro Use Guide
To explore the mechanism by which methohexital (MTH) activates epileptiform activity in patients with epilepsy, it was examined the effects of MTH on hippocampal CA1 and neocortical neurons via extracellular and whole-cell patch-clamp recordings in rat brain slices. Perfusion of slices with 10 to 100 microM MTH caused no significant change in glutamatergic transmission in the hippocampal CA1 region, but enhanced gamma-aminobutyric acid (GABA)A-mediated inhibitory postsynaptic currents and induced spontaneous inhibitory postsynaptic currents in neocortical and hippocampal CA1 neurons. In addition, MTH induced a tonic, bicuculline-sensitive hyperpolarization in association with increases in membrane conductance, suggesting a direct stimulation of GABAA receptors by MTH. Spontaneous epileptiform activity was not observed in the neocortex and hippocampus after exposure of slices to MTH, neither in the standard in vitro condition nor in the presence of 4-aminopyridine, which promotes rhythmic synaptic activities.
Name Type Language
METHOHEXITAL
INN   MART.   MI   USP   VANDF   WHO-DD  
INN  
Official Name English
2,4,6(1H,3H,5H)-PYRIMIDINETRIONE, 1-METHYL-5-(1-METHYL-2-PENTYNYL)-5-(2-PROPENYL)-, (+/-)-
Systematic Name English
METHOHEXITAL [MI]
Common Name English
(+/-)-5-ALLYL-1-METHYL-5-(1-METHYL-2-PENTYNYL)BARBITURIC ACID
Systematic Name English
METHOHEXITAL [WHO-DD]
Common Name English
METHOHEXITAL [INN]
Common Name English
METHOHEXITAL [USP]
Common Name English
METHOHEXITAL [MART.]
Common Name English
METHOHEXITAL [VANDF]
Common Name English
METHOHEXITAL CIV [USP-RS]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C67084
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
WHO-ATC N01AF01
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
WHO-VATC QN05CA15
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
WHO-VATC QN01AF01
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
NDF-RT N0000175693
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NDF-RT N0000008016
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
DEA NO. 2264
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
WHO-ATC N05CA15
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
Code System Code Type Description
ECHA (EC/EINECS)
205-798-6
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PRIMARY
USP_CATALOG
1413000
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PRIMARY USP-RS
IUPHAR
7233
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
PRIMARY
CAS
151-83-7
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
PRIMARY
DRUG CENTRAL
1748
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
PRIMARY
WIKIPEDIA
METHOHEXITAL
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
PRIMARY
DRUG BANK
DB00474
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
PRIMARY
PUBCHEM
9034
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PRIMARY
EVMPD
SUB14540MIG
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PRIMARY
RXCUI
6847
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
PRIMARY RxNorm
ChEMBL
CHEMBL7413
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PRIMARY
INN
807
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
PRIMARY
LACTMED
Methohexital
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
PRIMARY
NCI_THESAURUS
C66116
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
PRIMARY
MERCK INDEX
M7323
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
PRIMARY Merck Index
EPA CompTox
151-83-7
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PRIMARY
FDA UNII
E5B8ND5IPE
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PRIMARY
MESH
D008723
Created by admin on Sat Jun 26 06:56:43 UTC 2021 , Edited by admin on Sat Jun 26 06:56:43 UTC 2021
PRIMARY